Cell proliferation and death: Morphological evidence during corticogenesisin the developing human brain

Cell proliferation and death account for the refinement of the cell number during corticogenesis. These processes have been investigated in the human developing telencephalon (12th-24th week of gestation) and cerebellum (16th -24th week). Only foetal brains, which had normal neuropathological examina tion, were utilised. Cell proliferation was analysed by classical histology and PCNA immunohistochemistry; cell death was investigated by the TUNEL me thod, which makes evident the different stages of apoptosis. High figures o f mitotic nuclei were seen in the ventricular zone at the 12th-15th week of gestation, before sharply declining. The decrease of the proliferating cel ls occurs synchronously in both frontal and occipital germinal zones. Conve rsely, a slow increase of the number of the mitotic cells was observed in t he more dorsal regions, probably due to the presence of proliferating glial elements. The amount of apoptotic nuclei was always remarkably low in the transient compartments of the wall of the telencephalon. The moderate numbe r of apoptotic cells suggests that cellular mechanisms other than apoptosis are involved in the dissolution of the ventricular zone. Neither prolifera ting nor apoptotic cells were seen in the cortical plate. The topography of cell proliferation and death in the developing cerebellum did not account for a mutual relationship between the two events. The prolonged duration of the cell-cycle in the human developing CNS may explain its increased vulne rability to various DNA-damaging conditions, which can lead to either destr uctive lesions or malformations. (C) 1999 Wiley-Liss, Inc.